Professor Kefah Mokbel MB, BS, MS, FRCS

Gene Testing

This risk assessment depends upon the number and age of first-degree (mother, sisters, daughters) and second-degree (grandmothers, aunts, nieces) relatives who have had breast or ovarian cancer. The table below provides a guide to assessing breast cancer risk.

High Risk

Medium Risk

4+ relatives affected at any age (breast or ovarian cancer)
3 relatives affected before 40 years old (breast cancer)
3 relatives affected before 60 years old (breast or ovarian cancer)
2 first-degree relatives with both breast and ovarian cancer
Families with Li-Fraumeni syndrome
A family member with a positive test for breast cancer genes

1 first-degree relative with breast cancer before 40 years old
1 second-degree relative (P) with breast cancer before 40 years old
1 first-degree relative with bilateral breast cancer before 60 years old
2 first- or second-degree relatives with breast cancer before 60 years old or with ovarian cancer at any age
1 first- or second-degree relative with breast and ovarian cancer
1 first-degree male relative with breast cancer

Patients in the low-risk group (those having one first-degree relative with breast cancer occurring after the age of 50 years) can be looked after by their GP. They will require standard screening mammography every 18 months once they reach the age of 40. Regular self-examination of the breasts is also recommended.

Those women who have a moderate risk of developing breast cancer will be seen in the breast clinic and examined annually. They are advised to have yearly mammography between ages of 40 and 59 and, thereafter, at 18-month intervals.

High-risk women may carry the breast cancer genes BRCA-1, BRCA-2 PALB2, or PTEN. These women should be regularly screened for breast cancer from the age of 30 years or even earlier. Screening tools include clinical examination, high-resolution ultrasound scan, mammography (preferably digital) and more importantly magnetic resonance imaging (MRI). The latter has been shown recently to be more accurate than mammography and ultrasound in detecting breast cancer in high-risk young women and does not involve radiation exposure. However it is more likely to cause false alarms (called false positive results). In relation to high-risk women, it is important to bear in mind the following points:

They have a 50% chance of carrying the faulty gene(s).

If they do carry a gene, it does not mean that they will inevitably develop a breast cancer – only approximately 65% of carriers will develop breast cancer by the time that they reach their 80th year.

Screening for the faulty genes can easily be carried out if there are living affected relatives who will agree to provide blood samples.

Doctors are still not certain regarding what is the best course of action to take for an unaffected gene carrier.

Genetic Testing

Before genetic testing is considered, the patient must be counselled regarding the implications of both positive and negative test results, as each result has important implications. Those testing negative, i.e. who do not carry the faulty gene(s), frequently develop feelings of guilt for not having a condition that has affected close family members.

Once a patient has decided to proceed with a gene test, an affected relative is invited to provide a blood or saliva sample. Special scientific investigations are carried out on the DNA in the blood sample, looking for any abnormalities (mutations) in a panel of approximately 30 genes including BRCA-1 and BRCA-2. If the mutation is identified the patient who requested the gene test is then asked to give a blood or saliva sample to identify the potential gene.

All women with a newly diagnosed breast cancer should consider panel gene testing

Women with a family history can still have panel gene testing if an affected relative is not available for testing.

For more information on saliva genetic testing using the Color Cancer Panel of 30 genes

What Happens if the Gene Test is Positive?

Individuals testing positive for the breast cancer gene(s) have three options:

Regular clinical examinations and screening mammography on a yearly basis. This method allows earlier detection and treatment of breast cancer. Recent research suggests that magnetic resonance imaging (MRI) is superior to ultrasound and mammography in screening high-risk young women.

Surgery to remove both breasts and/or removal of the ovaries. This is an extreme choice but one that is very likely to prolong the survival of high-risk patients who carry a BRCA or PLAB2 gene mutation. Preventative mastectomy can reduce the risk of breast cancer in high-risk women by 90%. Preventative removal of both ovaries can also reduce the risk of breast cancer by 50% in gene carriers.

Several studies around the world have confirmed the role of certain drugs in preventing ER positive breast cancer. These drugs include tamoxifen, raloxifene and aromatase inhibitors. These drugs reduce the risk of developing breast cancer by approximately 50%, but there is concern regarding its potential side-effects and there is no evidence that they prolong survival.

For more information on risk reducing surgery for women carrying a BRCA gene mutation from articles written by Professor K. Mokbel

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A new article showcases the wide differences in BRCA testing protocols at labs around the world. The article surveyed 86 laboratories around the world about their BRCA testing practices and found that all the labs differed widely in their approach.